RGD Reference Report - Histone acetyltransferase MOZ acts as a co-activator of Nrf2-MafK and induces tumour marker gene expression during hepatocarcinogenesis. - Rat Genome Database

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Histone acetyltransferase MOZ acts as a co-activator of Nrf2-MafK and induces tumour marker gene expression during hepatocarcinogenesis.

Authors: Ohta, K  Ohigashi, M  Naganawa, A  Ikeda, H  Sakai, M  Nishikawa, J  Imagawa, M  Osada, S  Nishihara, T 
Citation: Ohta K, etal., Biochem J. 2007 Mar 15;402(3):559-66.
RGD ID: 2312274
Pubmed: PMID:17083329   (View Abstract at PubMed)
PMCID: PMC1863558   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20061194   (Journal Full-text)

HATs (histone acetyltransferases) contribute to the regulation of gene expression, and loss or dysregulation of these activities may link to tumorigenesis. Here, we demonstrate that expression levels of HATs, p300 and CBP [CREB (cAMP-response-element-binding protein)-binding protein] were decreased during chemical hepatocarcinogenesis, whereas expression of MOZ (monocytic leukaemia zinc-finger protein; MYST3)--a member of the MYST [MOZ, Ybf2/Sas3, Sas2 and TIP60 (Tat-interacting protein, 60 kDa)] acetyltransferase family--was induced. Although the MOZ gene frequently is rearranged in leukaemia, we were unable to detect MOZ rearrangement in livers with hyperplastic nodules. We examined the effect of MOZ on hepatocarcinogenic-specific gene expression. GSTP (glutathione S-transferase placental form) is a Phase II detoxification enzyme and a well-known tumour marker that is specifically elevated during hepatocarcinogenesis. GSTP gene activation is regulated mainly by the GPE1 (GSTP enhancer 1) enhancer element, which is recognized by the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2)-MafK heterodimer. We found that MOZ enhances GSTP promoter activity through GPE1 and acts as a co-activator of the Nrf2-MafK heterodimer. Further, exogenous MOZ induced GSTP expression in rat hepatoma H4IIE cells. These results suggest that during early hepatocarcinogenesis, aberrantly expressed MOZ may induce GSTP expression through the Nrf2-mediated pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Neoplasms  ISOKat6a (Rattus norvegicus)2312274; 2312274protein:increased expression:liver (rat)RGD 
Experimental Liver Neoplasms  IEP 2312274protein:increased expression:liver (rat)RGD 
hepatocellular carcinoma  ISOEp300 (Rattus norvegicus)2312274; 2312274protein:increased expression:liver (rat)RGD 
hepatocellular carcinoma  IEP 2312274protein:increased expression:liver (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of gene expression  IDA 2312274Gstp1RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIMafk (Rattus norvegicus)2312274 RGD 
RING-like zinc finger domain binding  IPIKat6a (Rattus norvegicus)2312274 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)
Kat6a  (lysine acetyltransferase 6A)
Mafk  (MAF bZIP transcription factor K)

Genes (Mus musculus)
Ep300  (E1A binding protein p300)
Kat6a  (K(lysine) acetyltransferase 6A)

Genes (Homo sapiens)
EP300  (E1A binding protein p300)
KAT6A  (lysine acetyltransferase 6A)


Additional Information